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J Virol, February 1998, p. 934-942, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Nitric Oxide Inhibits Rhinovirus-Induced Cytokine Production and
Viral Replication in a Human Respiratory Epithelial Cell Line
Scherer P.
Sanders,1,*
Edward S.
Siekierski,2
Jacqueline D.
Porter,2
Stephen M.
Richards,2 and
David
Proud2
Division of Pulmonary and Critical Care
Medicine1 and
Division of Allergy and Clinical
Immunology,2 Department of Medicine, The
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland
21224-6801
Received 19 June 1997/Accepted 5 November 1997
To better understand the early biochemical events that occur in
human rhinovirus (HRV) infections, we examined the kinetics and
mechanisms of interleukin-8 (IL-8) and IL-6 production from infected
epithelial cells. Several HRV strains caused IL-8 and IL-6 production,
but HRV-16 induced maximal IL-8 and IL-6 mRNA expression and protein
production more rapidly than did HRV-14, despite similar rates of
replication of the two viral strains. Viral induction of cytokine mRNA
does not require new protein synthesis, since it was unaffected by
cycloheximide treatment. The potent glucocorticoid budesonide did not
affect viral replication or cytokine mRNA induction but modestly
inhibited cytokine protein production. Interestingly, the nitric oxide
donor 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (NONOate)
inhibited both rhinovirus replication and cytokine production in a
dose-dependent fashion without reducing levels of cytokine mRNA. The
NONOate effects were due to release of nitric oxide, because NONOate
that had been depleted of its nitric oxide content had no effect. Thus,
nitric oxide may play an important anti-inflammatory and antiviral role
in colds and nitric oxide donors may represent a novel therapeutic
approach.
*
Corresponding author. Mailing address: Johns Hopkins
Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224-6801. Phone: (410) 550-2514. Fax: (410) 550-2612. E-mail: ssanders{at}welchlink.welch.jhu.edu.
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